Genetic Variants of Innate Immune Receptor May Increase Susceptibility for Depression

Genetic variants of an innate immune receptor that detects inflammation and tissue damage have been associated with HADS depression severity scores by a group of Hungarian researchers. These findings have implications for the function of brain-resident immune cells known as microglia and may contribute to the current understanding of genetic factors underlying the susceptibility for depression.

A group of Hungarian researchers investigated whether patients experiencing acute major depressive episodes carried different copies of the P2X7 receptor (purinergic receptor P2X, ligand-gated ion channel, 7) gene than healthy controls. The P2X7R, which is expressed by virtually all cells of the innate and adaptive immune systems, detects tissue damage and inflammation by sensing the extracellular presence of the energy-storing molecule ATP. Since depression may result from the abnormal stimulation of microglia, gene variants promoting the function of this immune-activating receptor could contribute to the onset and progression of disease.

The researchers conducted a case-controlled analysis of 315 inpatients with Major Depressive Disorder or Bipolar Disorder and 406 healthy control subjects. While the case-control study did not associate variants of the gene with depression, certain regions of the gene were shown to associate significantly with HADS (Hospital Anxiety and Depression Scale) depression severity scores, suggesting that patients with these genetic variants are more likely to develop certain symptoms of depression.

Pharmacologic methods for targeting and inhibiting this receptor have been developed and may become available to treat patients with depression and other neurological disorders.

Vereczkei A, Abdul-Rahman O, Halmai Z, et al. (2019) Association of purinergic receptor P2RX7 gene polymorphisms with depression symptoms. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 92:207-216.